PROJECT SUMMARY: CANCER IMMUNOLOGY (CI) Over the past decade, immunotherapy has emerged as an established modality that is revolutionizing the treatment of many cancers. The Cancer Immunology (CI) Research Program has focused on genetically manipulating T cells, applying new principles of synthetic biology, and combining engineered T cells with small molecules and antibodies to broaden the applications and improve the safety and efficacy of adoptive immunotherapy. Despite the success achieved with immunologic approaches in treating some malignancies, major gaps exist in our current understanding of the complex relationship between progressing tumors and host immunity, and these must be understood and overcome to achieve the potential of immunotherapy in many common cancers. The CI program will focus on systematically tackling these barriers to eradicating tumors using a variety of immunotherapeutic modalitie alone and in combination. The specific aims of CI are (1) to develop effective and safe cellular immunotherapies for adult and pediatric hematologic malignancies and solid tumors, (2) to identify and overcome the barriers to immune-mediated tumor eradication using clinical specimens and preclinical models, (3) to translate discoveries in basic immunology and synthetic biology to novel clinical applications in cancer immunotherapy. The Cancer Immunology (CI) program currently has 39 members from 11 departments and divisions and 4 Consortium institutions. Nineteen members have primary appointments at Fred Hutch, 12 members at University of Washington, and 8 members at Seattle Children?s. Fourteen new faculty members joined this program in the last cycle. The current research support of CI members is $23.4M (direct costs) in research grant funding, of which $4.4M (19%) is from the NCI and $7.8M (33%) is peer reviewed. The Cancer Immunology program published a total of 470 papers in the last grant period, of which 14% were intra- programmatic, 49% were inter-programmatic, and 50% had external co-authors. Program members have utilized all 12 of the Consortium Shared Resources. This P30 grant also assists this program by providing administrative and logistical support for CI meetings, pilot funding for new research projects, and recruitment resources for new faculty.